Effects of spatial dispersion of acetylcholine release on AV conduction responses to vagal stimulation in dogs.

We determined the effects on atrioventricular (AV) conduction of changing the spatial dispersion of acetylcholine (ACh) release from vagal nerve fibers in anesthetized dogs. We paced the atria at a constant rate and stimulated the vagus nerves with one stimulus burst per cardiac cycle. We varied the spatial heterogeneity of ACh release in the cardiac tissues by changing the stimulus voltage, and we varied the quantity of ACh release from each excited nerve fiber by changing the number of pulses per stimulus burst. We slightly changed the stimulus timing with each heartbeat to scan the entire cardiac cycle. We constructed phase-response curves (PRCs) by plotting the changes in AV conduction time as a function of the timing of vagal stimulation. We found that the amplitude of the PRC varied directly with average AV conduction time (AV), whereas the minimum-to-maximum phase difference of the PRC varied inversely with AV. However, for any given change in AV, the specific characteristics of the PRCs did not depend on whether we varied the number of pulses per burst or the stimulus voltage. Therefore, the phase-dependent characteristics of the dromotropic responses appear to be unaffected by the spatial dispersion of ACh release from the vagal nerve endings. The effects of vagal activity on the AV conduction time are determined by those conducting fibers that are the least restrained by neurally released ACh.